POS0503 RISKS OF CARDIOVASCULAR EVENTS AFTER THE INTRODUCTION OF bDMARDs IN NEWLY DIAGNOSED RHEUMATOID ARTHRITIS PATIENTS: A POPULATION-BASED INTERRUPTED TIME-SERIES ANALYSIS
Authors: Y. V. Zhou, D. Lacaille, N. Lu, J. Kopec, Y. Qian, B. Nosyk, J. A. Aviña-Zubieta, J. Esdaile, H. Xie
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is associated with increased risk of cardiovascular (CV) events. Biological disease-modifying anti-rheumatic drugs (bDMARDs) are effective in suppressing inflammation and preventing joint damage and may help lower the risk of CV events. However, recent epidemiological studies have shown mixed results with some suggesting a lower risk of CV events, while others reporting no significant differences. Objectives To determine the impact of the introduction of bDMARDs on incident cardiovascular disease (CVD) among patients newly diagnosed with RA compared with matched non-RA individuals. Methods In this age- and gender-matched cohort study using administrative health data for the population of BC, Canada, all incident RA patients diagnosed between 1995–2007 were identified. Non-RA individuals were randomly selected from the general control population to match with RA. Incident RA and non-RA individuals were then divided into quarterly cohorts according to their diagnosis date. The outcome of interest was incident CVD event after RA onset, which include acute myocardial infarction, cerebrovascular accident, and venous thromboembolism. We calculated the 8-year incident CVD rate for each cohort. We conducted interrupted time-series analyses to compare levels and trends of CVD in RA and non-RA individuals diagnosed during pre-bDMARDs (1995–2001) and post-bDMARDs (2003–2007) periods with intervention time set at year of 2002. Adjusted 8-year CVD rates for RA and non-RA cohorts diagnosed five years after bDMARDs introduction were compared with expected rates assuming no bDMARDs introduction, based on extrapolation of pre-bDMARDs trends. Results A total of 60,226 and 588,499 incident RA and non-RA individuals were identified. We identified 6,740 and 48,653 incident CVD events in total in RA and non-RA individuals, respectively. We observe no change in the secular trends of the 8-year CVD rates in both RA and non-RA individuals diagnosed in pre- and post-bDMARDS periods (Figure 1): the adjusted difference between the post- and pre-bDMARDs secular trends of 8-year CVD rates was 0.23 (p=0.26) for RA patients and -0.07 (p=0.33) for non-RA individuals (Table 1). However, we observed a reduction in the level of CVD rates among RA patients diagnosed in the post-bDMARDs period and no change in non-RA (Figure 1): the adjusted difference in level comparing points immediately before and after the intervention, and accounting for pre-intervention trend was -1.61 (p=0.03) in RA, while it was -0.02 (p=0.93) in non-RA (Table 1). Table 1. Results of interrupted time-series analysis of incident CVD rates, adjusting for age, gender, chronic obstructive pulmonary disease, Romano Charlson Comorbidity Index, diabetes, angina, hypertension, chronic kidney disease, peripheral vascular disease, atrial fibrillation, glucocorticoid, non-steroidal anti-inflammatory drugs, CVD medications, fibrates, contraceptives, and aspirin use at disease diagnosis year, using stepwise model selection Outcome Parameter RA Non-RA Unadj. Diff (95% CI) Adj. Diff (95% CI) Unadj. Diff (95% CI) Adj. Diff (95% CI) p-value p-value p-value p-value CVD Trend -0.15 (-0.72, 0.42) 0.6086 0.23 (-0.17, 0.64) 0.2620 -0.09 (-0.27, 0.08) 0.3084 -0.07 (-0.20, 0.07) 0.3290 Level (1 year post-intervention) -1.36 (-3.17, 0.45) 0.1474 -1.61 (-2.96, -0.25) 0.0251 0.22 (-0.41, 0.84) 0.5011 -0.02 (-0.44, 0.40) 0.9345 5 years post-intervention -1.96 (-4.48, 0.55) 0.1332 -0.67 (-2.80, 1.46) 0.5418 -0.15 (-1.06, 0.75) 0.7421 -0.29 (-0.97, 0.39) 0.4102 Figure 1. Unadjusted rates. Conclusion Arthritis onset after bDMARDs introduction is associated with a significant reduction in the risk of incident CVD events among RA patients, but not in the matched non-RA individuals. Acknowledgements We would like to thank the Ministry of Health of British Columbia and Population Data BC for providing access to the administrative data. All inferences, opinions, and conclusions drawn in this publication are those of the authors, and do not reflect the opinions or policies of the Data Stewards or the [British Columbia] Ministry of Health. No personal identifying information was made available as part of this study. Procedures used were in compliance with British Columbia’s Freedom in Information and Privacy Protection Act. Ethics approval was obtained from the University of British Columbia’s Behavioral Research Ethics Board (H15-00887). Disclosure of Interests None declared.